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Mechanisms of osteolytic bone metastases in breast carcinoma

  1. Sanna-Maria Käkönen Ph.D.,
  2. Gregory R. Mundy M.D.†,*

Article first published online: 23 JAN 2003

DOI: 10.1002/cncr.11132

Issue

Cancer

Cancer

Supplement: Skeletal Complications of Malignancy

Volume 97, Issue Supplement 3, pages 834–839, 1 February 2003

Additional Information

How to Cite

Käkönen, S.-M. and Mundy, G. R. (2003), Mechanisms of osteolytic bone metastases in breast carcinoma. Cancer, 97: 834–839. doi: 10.1002/cncr.11132

Author Information

  1. University of Texas Health Science Center, Department of Molecular Medicine, Institute for Drug Development, San Antonio, Texas

  1. †

    Fax: (210) 567-3803

*Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900

Publication History

  1. Issue published online: 23 JAN 2003
  2. Article first published online: 23 JAN 2003
  3. Manuscript Accepted: 1 NOV 2002
  4. Manuscript Received: 15 JUL 2002

Funded by

  • National Institutes of Health. Grant Number: CA40035
  • U.S. Army Department of Defense. Grant Number: DAMD17-99-1-9403

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Keywords:

  • bone metastases;
  • breast carcinoma;
  • osteolysis;
  • osteoclasts;
  • PTHrP;
  • TGFβ

Abstract

Osteolytic and osteoblastic metastases are often the cause of considerable morbidity in patients with advanced prostate and breast carcinoma. Breast carcinoma metastasis to bone occurs because bone provides a favorable site for aggressive behavior of metastatic cancer cells. A vicious cycle arises between cancer cells and the bone microenvironment, which is mediated by the production of growth factors such as transforming growth factor β and insulin growth factor from bone and parathyroid hormone-related protein (PTHrP) produced by tumor cells. Osteolysis and tumor cell accumulation can be interrupted by inhibiting any of these limbs of the vicious cycle. For example, bisphosphonates (e.g., pamidronate, ibandronate, risedronate, clodronate, and zoledronate) inhibit both bone lesions and tumor cell burden in bone in experimental models of breast carcinomametastasis. Neutralizing antibodies to PTHrP, which inhibit PTHrP effects on osteoclastic bone resorption, also reduce osteolytic bone lesions and tumor burden in bone. Other pharmacologic approaches to inhibit PTHrP produced by breast carcinoma cells in the bone microenvironment also produce similar beneficial effects. Identification of the molecular mechanisms responsible for osteolytic metastases is crucial in designing effective therapy for this devastating complication. Cancer 2003;97(3 Suppl):834–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11132

View Full Article (HTML) Get PDF (102K)